This laboratory's research program is focused on the genetics and cell and molecular biology of cardiovascular development. An integration of whole animal imaging, microscopy, and genomic and proteomic approaches are being utilized to elucidate the cell signaling pathways that regulate cardiovascular development. One project entail studies aimed at understanding the role of two extracardiac cell populations, the cardiac neural crest and the proepicardially derived cells, in the modulation of cardiovascular development and function. These studies will help elucidate cellular and molecular mechanisms that regulate outflow tract morphogenesis and coronary artery development. A second area of research interest is the cell signaling function of connexin gap junction protein, and its role in cardiovascular developoment. Previous work from the laboratory has indicated a novel role for connexins in regulating the migratory behavior of the cardiac neural crest and proepicardial cells. Present studies are focused on the protein-protein interactions that are essential in this connexin mediated cell signaling function. Both of these studies entail the use of transgenic and knockout mouse models, as well as in vitro primary cultured cells. A third project utilizes DNA resequencing chip together with dHPLC analysis to screen ENU mutagenized mice for connexin mutations. Phenotype analysis of mice harboring connexin mutations may provide novel insights into the role of connexin genes in cardiovascular development and function. In parallel to such mouse studies, DNA from human patients will be similarly analyzed to determine if connexin mutations may be linked to human cardiovascular defects and diseases. A fourth area of research focus involves the use of a discovery approach to identify novel genes and cell signaling pathways essential to the regulation of mammalian cardiovascular development. These studies entail the use of a combination of noninvasive ultrasound imaging to screen ENU mutagenized mice for cardiovascular defects, and the analyses of gene expression profiles in the developing embryo using gene chip microarrays. Such studies may help to identify novel genes and genetic pathways that are essential in the regulation of cardiovascular development and function.